The research outlined in this proposal seeks to define more precisely the relationship between the chemical structure of some O-alkyl O-substituted phenyl phenylphosphonothionates and their neurotoxic properties in chickens. Initially thirteen halogenated O-phenyl O-methyl phenylphosphonothionates will be synthesized to characterize the role of the halogenated leaving group on the neurotoxicity of the molecules. In addition, estimation of the inhibition of the neurotoxic esterases in vivo in poisoned chickens dosed orally and in vitro by the oxons of these organophosphorus compounds will be conducted by electrophoretic methods. Finally, C14-labeled neurotoxic esters will be synthesized to estimate quantitatively the degree of inhibition of the neurotoxic esterase as well as evaluate the metabolic pathways of these compounds in the chicken.